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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li yongchang wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly understood.Here,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics data.As a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC.Among the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in cancer.Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras signaling.Next,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls.Mechanistically,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC risk.In summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis

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Chinese Medical Journal 2024年第4期137卷 431-440页

作者： Danyi Zou Yimin Cai Meng Jin Ming Zhang Yizhuo Liu Shuoni Chen Shuhui Yang Heng Zhang Xu Zhu Chaoqun Huang Ying Zhu Xiaoping Miao yongchang wei Xiaojun Yang Jianbo Tian Department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Epidemiology and Biostatistics School of Public HealthTaiKang Center for Life and Medical SciencesWuhan UniversityWuhanHubei 430071China Department of Gastrointestinal Oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430071China Department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanHubei 430071China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Sciences and TechnologyWuhanHubei 430030China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great importance.This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods:We first systematically performed expression quantitative trait locus(eQTL)analysis using The Cancer Genome Atlas(TCGA)dataset.Then,the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets(TCGA and GSE39582 dataset from the Gene Expression Omnibus database).The seven most potentially functional eQTL single nucleotide polymorphisms(SNPs)associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data.The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results:The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1(ERAP1)was significantly associated with the prognosis of CRC(additive model,hazard ratio[HR]:1.43,95%confidence interval[CI]:1.08-1.88,P=0.012).The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3(TCF3)and subsequently reduce the expression of ERAP1.The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.Conclusion:The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.Trial Registration:No.NCT00454519(https://clinicaltrials.gov/)

关键词： Colorectal cancer Prognosis Genetic variation Quantitative trait loci TCF3 rs71630754 Single nucleotide polymorphisms

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Nanofluidic memristor based on the elastic deformation of nanopores with nanoparticle adsorption

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National Science Review 2024年第4期11卷 46-54页

作者： Xi Zhou Yuanyuan Zong yongchang Wang Miao Sun Deli Shi wei Wang Guanghua Du Yanbo Xie Department of Chemistry and Chemical Engineering Northwestern Polytechnical University School of Physical Science and Technology Northwestern Polytechnical University School of Aeronautics and Institute of Extreme Mechanics Northwestern Polytechnical University Institute of Modern Physics Chinese Academy of Sciences

The memristor is the building block of neuromorphic computing. We report a new type of nanofluidic memristor based on the principle of elastic strain on polymer nanopores. With nanoparticles absorbed at the wall of a single conical polymer nanopore, we find a pinched hysteresis of the current within a scanning frequency range of 0.01–0.1 Hz, switching to a diode below 0.01 Hz and a resistor above 0.1 Hz. We attribute the current hysteresis to the elastic strain at the tip side of the nanopore, caused by electrical force on the particles adsorbed at the inner wall surface. Our simulation and analytical equations match well with experimental results, with a phase diagram for predicting the system transitions. We demonstrate the plasticity of our nanofluidic memristor to be similar to a biological synapse. Our findings pave a new way for ionic neuromorphic computing using nanofluidic memristors.

关键词： nanofluidics memristor neurocomputing elastic deformation

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AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第3期24卷 232-247页

作者： Yi LI Wenyan SHE Xiaoran XU Yixin LIU Xinyu WANG Sheng TIAN Shiyi LI Miao WANG Chaochao YU Pan LIU Tianhe HUANG yongchang wei Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversityHubei Cancer Clinical Study Center&Hubei Key Laboratory of Tumor Biological BehaviorsWuhan 430071China College of Chemistry and Molecular Science Wuhan UniversityWuhan 430071China Department of Integrated Chinese and Western Medicine Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China

Drastic surges in intracellular reactive oxygen species(ROS)induce cell apoptosis,while most chemotherapy drugs lead to the accumulation of ROS.Here,we constructed an organic compound,arsenical N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2),which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer(GC).Mechanistically,by targeting pyruvate dehydrogenase kinase 1(PDK1),AAZ2 caused metabolism alteration and the imbalance of redox homeostasis,followed by the inhibition of phosphoinositide-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway and leading to the activation of B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)/caspase-9(Cas9)/Cas3 cascades.Importantly,our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft.Overall,our data suggested that AAZ2 could contribute to metabolic abnormalities,leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

关键词： N-(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide(AAZ2) Gastric cancer Reactive oxygen species(ROS) Apoptosis Pyruvate dehydrogenase kinase 1(PDK1) Glucose metabolism

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9Cr-1.5W-0.15Ta耐热钢搅拌摩擦焊焊缝组织和冲击性能分析

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焊接学报 2024年第4期45卷 36-42,I0005页

作者：张超周猛兵崔雷陶欣王军王伟刘永长中国核动力研究设计院第四研究所成都610213 天津大学天津市现代连接技术重点实验室天津300354 天津大学水利安全与仿真国家重点实验室天津300354

对9Cr-1.5W-0.15Ta耐热钢搅拌摩擦焊焊缝的微观组织演变和冲击性能进行了分析.结果表明,由于搅拌针剧烈的机械搅拌和焊接热循环的双重作用,搅拌摩擦焊缝区域内发生晶粒破碎、完全奥氏体化动态再结晶、晶界处M23C6相溶解和晶内M3C相析出... 详细信息

对9Cr-1.5W-0.15Ta耐热钢搅拌摩擦焊焊缝的微观组织演变和冲击性能进行了分析.结果表明,由于搅拌针剧烈的机械搅拌和焊接热循环的双重作用,搅拌摩擦焊缝区域内发生晶粒破碎、完全奥氏体化动态再结晶、晶界处M23C6相溶解和晶内M3C相析出,焊后较大的冷却速率抑制晶粒长大,促进了马氏体转变.在−100~20℃温度内进行了冲击试验,随着冲击试验温度的增加,母材和FSW焊缝的冲击吸收能量均表现为单调增大的特征,同时冲击断裂模式由脆性断裂逐渐转变为延性断裂.由于FSW焊缝中板条马氏体的形成、“针状”M3C碳化物的析出,FSW焊缝的硬度显著增大,并且在相同温度下FSW焊缝的冲击韧性发生降低,韧—脆转变温度由母材的−50℃升高至−40.2℃.

关键词： 9Cr-1.5W-0.15Ta耐热钢搅拌摩擦焊微观组织冲击韧性韧—脆转变温度

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格栅节点加强对风积沙筋土界面力学性能的影响

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中南大学学报（自然科学版） 2024年第1期55卷 172-187页

作者：杜炜聂如松谭永长张杰祁延录赵春彦中南大学土木工程学院湖南长沙410075 中南大学重载铁路工程结构教育部重点实验室湖南长沙410075 新疆铁道勘察设计院有限公司新疆乌鲁木齐830011

在普通双向土工格栅上附加节点,可形成具有立体加筋效果的加强节点土工格栅。在普通双向土工格栅加筋风积沙拉拔试验和离散元数值模型的基础上,构建加强节点土工格栅加筋风积沙的三维离散元拉拔模型,研究加强节点排布方式、厚度、数量... 详细信息

在普通双向土工格栅上附加节点,可形成具有立体加筋效果的加强节点土工格栅。在普通双向土工格栅加筋风积沙拉拔试验和离散元数值模型的基础上,构建加强节点土工格栅加筋风积沙的三维离散元拉拔模型,研究加强节点排布方式、厚度、数量、相邻节点间距对筋土界面力学性能的影响。研究结果表明:在节点上侧加强、节点下侧加强和节点上、下两侧同时加强的排布方式中,上下两侧同时加厚对极限拉拔阻力和界面摩擦角的增幅最大;加强节点可优化土工格栅的加筋性能;当节点布置方式不变时,加强节点厚度和节点数量均与极限拉拔阻力增量呈现出良好的线性相关性;与普通土工格栅相比,加强节点土工格栅的剪切带范围更大,且限制土体位移的能力更强;当多个节点同时工作且相邻节点的间距较小时,相邻节点的影响区域互相重叠,使节点提供的极限拉拔阻力增量降低,产生节点群体效应;随着相邻节点的间距增大,节点影响区域的重叠范围减少,群体效应逐渐减弱。

关键词：土工格栅风积沙拉拔试验加强节点离散元

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二氧化碳海洋封存的技术和研究现状

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海洋科学 2024年第4期48卷 108-121页

作者：张海滨卢迪王永昌田文爽沈国飞宋学行魏伟海油总节能减排监测中心有限公司天津300452 中国科学院上海高等研究院中国科学院低碳转化科学与工程重点实验室上海201210

全球变暖的问题正变得日益严峻,碳减排碳中和已成为国际社会的共识和努力目标。作为CO_(2)减排的重要方式之一,二氧化碳捕集、利用与封存(Carbon Capture,Utilization and Storage,CCUS)近年来备受关注并且发展迅猛。CO_(2)海洋封存作... 详细信息

全球变暖的问题正变得日益严峻,碳减排碳中和已成为国际社会的共识和努力目标。作为CO_(2)减排的重要方式之一,二氧化碳捕集、利用与封存(Carbon Capture,Utilization and Storage,CCUS)近年来备受关注并且发展迅猛。CO_(2)海洋封存作为其中一种最具潜力的减排方式,了解其发展现状对进一步研究CO_(2)封存具有重要的参考价值。本文介绍了CO_(2)海洋封存的方法和封存机理,总结了该技术在国内外研究进展。此外,文章还概述了我国在CO_(2)海洋封存上的巨大潜力和库源匹配上的优势,以及海洋封存对环境可能造成的影响。最后,指出推进CO_(2)海洋封存技术的研究并开发相应的能力,将有助于加速推进碳减排进程、尽快实现碳中和目标。

关键词：二氧化碳捕集、利用和封存海洋封存研究进展海洋环境海洋酸化

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智能推荐系统在金融领域的应用

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金融科技时代 2024年第4期32卷 59-63页

作者：龚永昌高龙韦东东中原银行数智金融创新实验

随着客户的金融需求逐渐多元化,如何为千万级的零售客户提供个性化的金融服务成为了金融领域的新课题。针对传统推荐算法难以解决银行产品推荐结构趋向同质化、泛化性差等问题,文章提出一种面向金融领域的智能推荐算法框架。对比基线,... 详细信息

随着客户的金融需求逐渐多元化,如何为千万级的零售客户提供个性化的金融服务成为了金融领域的新课题。针对传统推荐算法难以解决银行产品推荐结构趋向同质化、泛化性差等问题,文章提出一种面向金融领域的智能推荐算法框架。对比基线,该项目的推荐效果显著提高,召回率recall@1从22.2%提升至41.1%,线上产品销量提升56%。

关键词：金融科技个性化推荐人工智能

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Prediction of M–A Constituents and Impact Toughness in Stir Zone of X80 Pipeline Steel Friction Stir Welds

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金属学报:英文版 2023年第4期36卷 573-585页

作者： Xueli Wang Xin Ji Bin He Dongpo Wang Chengning Li yongchang Liu wei Guan Lei Cui Tianjin Key Laboratory of Advanced Joining Technology School of Materials Science and EngineeringTianjin UniversityTianjin 300354China

This study explored a strategy for predicting the proportion of martensite–austenite(M–A)constituents and impact toughness of stir zone(SZ)on X80 pipeline steel joints welded by friction stir welding(FSW).It is found that the welding forces,including the traverse force(F_(x)),the lateral force(F_(y))and the plunge force(F_(z)),are the key variables related to the change of welding parameters and influence remarkably the characteristics of M–A constituents and impact toughness of SZ.The impact toughness of SZ is commonly lower than that of the base material due to the formation of lath bainite and coarsening of austenite.The characteristics of M–A constituents in SZ are sensitive to the variation of welding parameters and respond well to the change of welding forces.The proportion of small island M–A constituents increases with the decrease in rotational speed and the increase in Fz.The increase in the amount of island M–A constituents is beneficial to improve the impact toughness of SZ.Based on the above findings,a machine learning(ML)model for predicting the M–A constituents and impact toughness is constructed using the force features as the input data set.The force data-driven ML model can predict the M–A constituents and impact toughness precisely and exhibits higher accuracy than ML built with welding parameters.It is believed that the high accuracy is achieved because the force features include more details of FSW process,such as the heat generation,material flow,plastic deformation,and so on,which govern the microstructural evolution of SZ during FSW.

关键词： Friction stir welding Pipeline steel Welding force M-A constituents Impact toughness

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Genome-wide transcriptome analysis of porcine epidemic diarrhea virus virulent or avirulent strain-infected porcine small intestinal epithelial cells

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Virologica Sinica 2022年第1期37卷 70-81页

作者： Ouyang Peng Xiaona wei Usama Ashraf Fangyu Hu Yongbo Xia Qiuping Xu Guangli Hu Chunyi Xue yongchang Cao Hao Zhang State Key Laboratory of Biocontrol Life Sciences SchoolSun Yat-sen UniversityGuangzhou510006China Wen's Group Academy Wen's Foodstuffs Group CoLtdXinxingGuangdong527400China State Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhan430070China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou510120China

Porcine epidemic diarrhea virus(PEDV)is the main cause of diarrhea,vomiting,and mortality in pigs,which results in devastating economic loss to the pig industry around the globe.In recent years,the advent of RNAsequencing technologies has led to delineate host responses at late stages of PEDV infection;however,the comparative analysis of host responses to early-stage infection of virulent and avirulent PEDV strains is currently unknown.Here,using the BGI DNBSEQ RNA-sequencing,we performed global gene expression profiles of pig intestinal epithelial cells infected with virulent(GDS01)or avirulent(HX)PEDV strains for 3,6,and 12 h.It was observed that over half of all significantly dysregulated genes in both infection groups exhibited a down-regulated expression pattern.Functional enrichment analyses indicated that the differentially expressed genes(DEGs)in the GDS01 group were predominantly related to autophagy and apoptosis,whereas the genes showing the differential expression in the HX group were strongly enriched in immune responses/inflammation.Among the DEGs,the functional association of TLR3 and IFIT2 genes with the HX and GDS01 strains replication was experimentally validated by TLR3 inhibition and IFIT2 overexpression systems in cultured cells.TLR3 expression was found to inhibit HX strain,but not GDS01 strain,replication by enhancing the IFIT2 expression in infected cells.In conclusion,our study highlights similarities and differences in gene expression patterns and cellular processes/pathways altered at the early-stage infection of PEDV virulent and avirulent strains.These findings may provide a foundation for establishing novel therapies to control PEDV infection.

关键词： Coronavirus Porcine epidemic diarrhea virus(PEDV) Virulence Transcriptome Apoptosis Autophagy Immunity

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